Depending on the type of alpha-AR blockage used in combination with dutasteride, there is a difference in serum PSA decrease rate, prostate volume reduction rate, and persistence rate. ~Comparison of long-term effects over 3 years ~

Magari T1, Sekiguchi Y1, Furuya Y1, Oki R1, Ogura H1, Ito K1, Kurosawa I1

Research Type


Abstract Category

Male Lower Urinary Tract Symptoms (LUTS) / Voiding Dysfunction

Abstract 685
Urology - Best of the Rest
Scientific Podium Short Oral Session 32
Friday 6th September 2019
16:07 - 16:15
Hall H2
Benign Prostatic Hyperplasia (BPH) Bladder Outlet Obstruction Male Retrospective Study
1.Department of Urology, Kurosawa Hospital,Takasaki,Japan

Tomohiro Magari



Hypothesis / aims of study
Dutasteride (DUT) reduces prostate volume and improves LUTS by releasing the mechanical obstruction in the prostatic urethra. This drug is often used with alpha-AR blockage different in action mechanism. Several kinds of alpha-AR blockage is used, however the report that compared the effect every drug has not been published as far as our knowledge. The report that Inhibit prostate cancer cell growth by several alpha-AR blockage has been published 1,2), however, there are very few reports that naftopidil inhibit prostate growth in BPH patients 3). Therefore effect may vary according to a combination drug. We have examined 12 months changes using DUT and several kinds of alpha-AR blockage in the past.In this study, we examined long-term changes of the prostate volume (PV), post void residual (PVR), and serum PSA levels for 3 years using DUT and several kinds of alpha-AR blockage for patients who complain of LUTS associated with BPH.
Study design, materials and methods
We included for 404 cases diagnosed BPH and performed combination therapy with DUT and alpha-AR blockage. DUT 0.5mg was administered once a day for over 36 months continuously. We divided alpha-AR blockage into tamsulosin (TAM), naftopidil (NAF), silodosin (SIL), and we compared the effect. We examined changes of the PV (3,6,12,24,36M), PVR (3,6,12,24,36M), and serum PSA levels (6,12,24,36M) using DUT and several kinds of alpha-AR blockage to the patients, complaining of LUTS associated with BPH. In addition, we examined the duration of each groups for up to 3 years.
The classification of cases was TAM 51cases, NAF 70 cases, and SIL 283 cases. Background of alpha-AR blockage use case was shown median (range), TAM was age 78 (54-97), PSA 4.1 (0.5-21.1) ng/mL, PV 53.3 (22.1-149.0) mL, PVR 19.9 (0-238.0) mL, NAF was 77 (56-93), 4.1 (0.2-46.3) ng/mL, 57.5 (24.2-181.0) mL, 26.0 (0-249.0) mL, and SIL was 75 (53-96), 5.1 (0.7-28.9) ng/mL, 62.8 (26.0-245.3) mL, 86.1 (0-479.0) mL. Compared with TAM and NAF, SIL significantly increased PVR (p<0.01). The rate of change of serum PSA in each groups were significantly decreased (p<0.001) at 6,12,24, and 36M, respectively. Compared with TAM, NAF and SIL were significantly decreased (p<0.05) at 12M (-44.9±23.8, -58.2±15.2, and -55.9±18.0%) (Fig. 1). The rate of change of PV in each groups were significantly decreased (p<0.001) at 6,12,24, and 36M, respectively. Compared with NAF and SIL, TAM was significantly decreased (p<0.05) at 3M (-21.2±10.6, -14.9±13.5, and -16.1±11.4%) and 6M (-26.9±12.4, -19.8±12.3, and -20.2±12.1%) (Fig. 2). PVR in each groups were discussed the change from the baseline. TAM was significantly decreased at 3 (p<0.01),6 (p<0.05),12 (p<0.01), and 36M (p<0.05), and SIL was significantly decreased at 3,6,12,24, and 36M (p<0.001) respectively. The duration of each groups for up to 3 years were 19.4±12.9, 22.5±13.2, and 24.5±13.1M. Compared with TAM, SIL was significantly longer (p<0.05).
Interpretation of results
In the present study, TAM was strong in prostate volume reduction effect, while PSA lowering effect was stronger in NAF and SIL. This result may be related to prostatic cell atrophy effect including cancer cells in NAF and SIL. However, when observed for a long time, However, the difference between each group decreases, and the difference in efficacy between drugs may be small if the case can be continued for a long period of time.
Concluding message
This is the first report to examine the changes not only PV but also serum PSA values by combination therapy with DUT and alpha-AR blockage, particularly comparison of the effect several kinds of alpha-AR blockage for up to 3 years. From this examination, it was suggested that a difference might be recognized in degree of PSA decrease and the prostatic reduction by a concomitant drug. It was thought that prospective study was necessary to perform a close comparison.
Figure 1
Figure 2
  1. Kawahara T, Aljarah AK, Shareef HK, Inoue S, Ide H, Patterson JD, Kashiwagi E, Han B, Li Y, Zheng Y and Miyamoto H: Silodosin inhibits prostate cancer cell growth via ELK1 inactivation and enhances the cytotoxic activity of gemcitabine.Prostate 76: 744-756, 2016.
  2. Yamada D, Nishimatsu H, Kumano S, Hirano Y, Suzuki M, Fujimura T, Fukuhara H, Enomoto Y, Kume H and Homma Y: Reduction of prostate cancer incidence by naftopidil, an a1 -adrenoceptor antagonist and transforming growth factor-ß signaling inhibitor. Int J Urol 20: 1220-1227, 2013.
  3. Kojima Y, Sasaki S, Oda N, Koshimizu TA, Hayashi Y, Kiniwa M, Tsujimoto G and Kohri K: Prostate growth inhibition by subtype-selective alpha(1)-adrenoceptor antagonist naftopidil in benign prostatic hyperplasia. Prostate 69: 1521-1528, 2009.
<span class="text-strong">Funding</span> In this examination, we do not receive the subsidy at all. <span class="text-strong">Clinical Trial</span> No <span class="text-strong">Subjects</span> Human <span class="text-strong">Ethics Committee</span> Kurosawa Hospital Ethical Review Board <span class="text-strong">Helsinki</span> Yes <span class="text-strong">Informed Consent</span> Yes